Drug Interaction Report

MONITOR: Coadministration with lenacapavir may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. According to the manufacturer, lenacapavir is a moderate inhibitor of CYP450 3A4 and due to its long half-life after subcutaneous administration, it may increase the exposure to and risk of adverse reactions to drugs primarily metabolized by CYP450 3A4 that are initiated within 9 months after the last subcutaneous lenacapavir dose. In pharmacokinetic studies in fed subjects without HIV, coadministration of oral lenacapavir (600 mg twice daily for 2 days, then a single 600 mg dose) with the sensitive CYP450 3A4 substrate midazolam (single 2.5 mg dose orally at the same time as the single lenacapavir dose) led to an increase in midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.9-fold and 3.6-fold, respectively.

MANAGEMENT: Caution is advised if lenacapavir is coadministered with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic index. Due to its long half-life, the effect may persist for up to 9 months after the last subcutaneous dose, so caution and monitoring for adverse effects are also advised during this time. The prescribing information for the coadministered drug should also be consulted for specific dosing recommendations.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zopiclone and eszopiclone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of eszopiclone (the S-enantiomer of zopiclone) with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In healthy adults, administration of a 3 mg dose of eszopiclone after a high-fat meal decreased the mean peak plasma drug concentration (Cmax) by 21% and delayed the time to reach peak plasma drug concentration (Tmax) by approximately 1 hour. Theoretically, this interaction should also affect racemic zopiclone.

MANAGEMENT: Patients receiving zopiclone or eszopiclone should be advised to avoid consumption of alcohol. For faster sleep onset, it may be advisable to not administer eszopiclone and zopiclone with or immediately after a high-fat/heavy meal.